Amiloride: effects on myocardial force of contraction, sodium pump and Na+/Ca2+ exchange

The direct effects of amiloride on myocardial contractility were examined in electrically stimulated left atrial muscle of guinea-pig heart. Amiloride (0.3 to 1.5 mM) produced a positive inotropic effect which, at higher concentrations, was followed by a decline in developed tension. These effects were not accompanied by contracture or arrhythmia and were not affected by a combination of phentolamine, nadolol, cimetidine, tripelennamine and atropine. The above concentrations of amiloride prolonged the action potential duration during the development of the positive inotropic effect; however, no further change in the action potential duration was observed during the decline in developed tension caused by high concentrations of amiloride. Myocardial membrane Na,K-ATPase, ouabain-sensitive 86Rb+ uptake and Na+-dependent Ca2+ efflux from sarcolemmal membrane vesicles were all inhibited by amiloride. The positive inotropic effect of the agent is reduced and the negative inotropic action is enhanced in low Na+ solutions, i.e., under conditions likely to favor Ca2+ influx via Na+/Ca2+ exchange. These results suggest that amiloride, under the present conditions, has a complex interaction with cardiac muscle fibers. Amiloride may produce its inotropic effects in guinea-pig atrial muscle by several mechanisms including sodium pump inhibition, Na+/Ca2+ exchange inhibition, prolongation of the action potential duration, and/or actions such as Na+/H+ exchange inhibition which were not directly addressed in this study.     

Current Concepts in the Treatment of Resectable Pancreatic Cancer

Purpose of Review

The diagnosis of pancreatic cancer carries with it a high mortality rate. Despite advances in the field, this has remained relatively unchanged over the last few decades. Current options for the treatment of resectable pancreatic ductal adenocarcinoma will be reviewed here in conjunction with the historical data that support them. We will focus on updates in treatment guidelines and ongoing clinical trials of interest.

Recent Findings

For localized disease, standard of care includes resection followed by adjuvant chemotherapy ± chemoradiation. Recently, a report was published supporting the use of doublet therapy with gemcitabine and capecitabine (as opposed to gemcitabine monotherapy), which prompted a practice-changing update to major treatment guidelines. Multiple trials using neoadjuvant treatment, novel therapies, and different forms of radiation are ongoing.

Summary

Although pancreatic cancer is an active area of research, outcomes remain dismal. Clinical trials will need to be more robust and innovative to drastically improve survival statistics.

     

Vereinbarung eines Ausfallhonorars bei Nichteinhaltung eines Behandlungstermins

Abstrakt Die wirksame Vereinbarung eines Ausfallhonorars setzt voraus, dass dem Patienten eine Entlastungsm?glichkeit für unverschuldetes Nichterscheinen einger?umt wird. (Leitsatz der Bearbeiterin)     

Cutaneous photoaging treated with a combined 595/1064 nm laser.

BACKGROUND AND OBJECTIVES: The pulsed dye laser (PDL) has been used for a variety of vascular changes associated with photoaging. The Nd:YAG laser has been shown to be effective in the treatment of deeper facial vessels, as well as to stimulate new dermal collagen deposition. This study was undertaken to evaluate the safety and efficacy of sequential dual-wavelength PDL and Nd:YAG laser treatment of photoaged facial skin. METHODS: Fifteen individuals, between the ages of 38 and 66 years old, with various stigmata of facial photoaging, were entered into the study. Five sequential combined PDL/Nd:YAG (Cynergy, Cynosure Inc., Westford, MA, USA) treatments were performed using a 10-mm handpiece at monthly intervals. PDL parameters included a 10-ms pulse duration and a fluence set at 1 J/cm2 below the purpura threshold. Nd:YAG parameters were set at a 50-ms pulse duration with fluences varying between 35 and 50 J/cm2, depending on patient comfort. Improvement was determined by evaluation of photographs taken before the first treatment and at 1 and 3 months following the last treatment, as well as the individual's self-assessment. RESULTS: Individuals tolerated treatments well with no serious, long-term, or permanent adverse effects. Improvement was most pronounced in telangiectasias and diffuse erythema, followed by epidermal dyspigmentation and lentigines. Some individuals were also noted to have improved smoothness, radiance, or pore size. The improvement was generally maintained at the 3-month follow-up. In addition, the average self-reported improvement was 1.7 (on a 0-4 scale) at 1 month and 2.4 at 3 months following the last treatment. CONCLUSION: A novel combined sequential PDL/Nd:YAG laser can be used to treat a variety of cutaneous changes associated with photoaging. Further studies may determine the relative impact of each laser and whether the total effect is simply additive or synergistic     

Determinants of improvement in quality of life of alcohol-dependent patients during an inpatient withdrawal programme

Background: To investigate the improvement in quality of life (QoL) of alcohol-dependent patients during a 3-week inpatient withdrawal programme, and to identify the sociodemographic, clinical and alcohol-related variables associated with baseline QoL on admission and with improvement of QoL during residential treatment.     

Delayed function reduces renal allograft survival independent of acute rejection

BACKGROUND: Mechanisms by which delayed allograft function reduces renalallograft survival are poorly understood, This study evaluatedthe relationship of delayed allograft function to acute rejectionand long-term survival of cadaveric allografts. METHODS: 338 recipients of cadaveric allografts were followed until death,resumption of dialysis, retransplantation, loss to follow-up,or the study's end, whichever came first. Delayed allograftfunction was defined by dialysis during the first week followingtransplantation, Multivariate Cox proportional hazards survivalanalysis was used to assess the relationship of delayed allograftfunction to rejection and allograft survival. RESULTS: Delayed allograft function, recipient age, preformed reactiveantibody levels, prior kidney transplantation, recipient race,rejection during the first 30 days and rejection subsequentto 30 days following transplantation were predictive of allograftsurvival in multivariate survival models. Delayed allograftfunction was associated with shorter allograft survival afteradjustment for acute rejection and other covariates (relativerate of failure [RR]=1.72 [95% CI, 1.07, 2.76]). The adjustedRR of allograft failure associated with any rejection duringthe first 30 days was 1.99 (1.23, 3.21), and for rejection subsequentto the first 30 days was 3.53 (2.08, 6.00). The impact of delayedallograft function did not change substantially (RR=1.84 [1.15,2.95]) in models not controlling for acute rejection. Theseresults were stable among several subgroups of patients andusing alternative definitions of allograft survival and delayedallograft function. CONCLUSIONS: This study demonstrates that delayed allograft function andacute allograft rejection have important independent and deleteriouseffects on cadaveric allograft survival. These results suggestthat the effect of delayed allograft function is mediated, inpart, through mechanisms not involving acute clinical rejection.